Bone marrow endosteum in homeostasis and metastasis

The endosteum is a thin layer of connective tissue lining the inner surfaces of bones adjoining the medullary cavity. The endosteum houses a variety of cells crucial for bone growth, repair and remodelling, including bone-forming osteoblasts, bone-resorbing osteoclasts and their precursor cells. Historically, the endosteum has been extensively studied as a key site for haematopoiesis by which blood cells are incessantly produced. However, recent studies have defined the endosteum as a niche for skeletal stem cells, underscoring the importance of the harmony between the inner endosteum and the outer periosteum in maintaining bone homeostasis. The endosteum also plays a significant role in pathological conditions, as it is recognized as a preferential site for bone metastasis of several common carcinomas, including breast and prostate cancers. The uniquely complex microenvironment of the endosteum favours the survival of cancer cells, contributing to dormancy, resistance to therapies and eventually, reemergence and progression. In this review, we discuss the multifaceted functions of the bone marrow endosteum, focusing on its dual roles in normal bone haematopoiesis and tumour metastasis.